New AACR Journal, Blood Cancer Discovery, Publishes Its First Paper

Study reports the landscape of mutations present in pediatric acute lymphoblastic leukemia (ALL) and how this landscape changes during treatment, leading to relapse

PHILADELPHIA — The American Association for Cancer Research (AACR) today announced that its latest journal, Blood Cancer Discovery, has published its first accepted article online. Blood Cancer Discovery is the ninth journal in the AACR’s prestigious portfolio of scientific publications.

According to Riccardo Dalla-Favera, MD, co-editor-in-chief, “The field of hematologic malignancies has historically been at the forefront of seminal discoveries, including those that have played a major role in innovative research in other tissue and tumor types. Given the multidisciplinary scientific programs of the AACR, the launch of this latest journal provides an excellent opportunity to bring together researchers from numerous fields in order to accelerate the rate at which science can impact patient care. To this end, Blood Cancer Discovery will identify and showcase the most compelling work in the field.”

The first paper published in Blood Cancer Discovery is titled “Mutational landscape and patterns of clonal evolution in relapsed pediatric acute lymphoblastic leukemia.”

“This study is the most comprehensive analysis of the genome of childhood ALL at several steps during treatment and at relapse. For this reason, we are confident it will become a classic in the field,” said Kenneth C. Anderson, MD, co-editor-in-chief of Blood Cancer Discovery.

“ALL is one of the most common causes of death from cancer for children in the United States,” said study author Charles G. Mullighan, MD, member of the Department of Pathology and deputy director of the St. Jude Children’s Research Hospital Comprehensive Cancer Center in Memphis. “Our study provides a tapestry of the genetic changes in pediatric ALL and how these genetic changes alter over time as the patient is treated and as the leukemia relapses. This information has the potential to be translated into new strategies for early detection of relapse and the development of treatments to prevent clinical occurrence.”

Mullighan and colleagues comprehensively analyzed a series of leukemia cell samples from 92 children with relapsed ALL, 67 with B-cell ALL and 25 with T-cell ALL. Samples were obtained at diagnosis, at several times during treatment, and at the point of relapse. Samples were analyzed using a number of different techniques, including exome, genome, and transcriptome sequencing, digital-droplet PCR, and xenografting.

The researchers identified 50 significantly mutated genes at relapse and multiple patterns of clonal evolution, including genes that are mutated at diagnosis and enriched at relapse, and other genes that are only mutated after initial diagnosis. Among the changes detected over time was an increase in RAS pathway mutations at B-cell ALL relapse. RAS pathway mutations accounted for 17.9 percent of the mutations in patients at diagnosis, and 31.3 percent of the mutations at relapse. In T-cell ALL, PI3K-AKT pathway mutations were common in patients at diagnosis and were infrequently detected at relapse.

Mullighan highlighted three parts of the study as having the potential for clinical translation:

• distinguishing between relapse and second primary leukemias;
• identification of a subset of hypermutated leukemias; and
• early detection of relapse-driving mutations using digital-droplet PCR.

“This inaugural paper reflects the high caliber of articles to be included in Blood Cancer Discovery,” said Margaret Foti, PhD, MD (hc), chief executive officer of the AACR. “Editors-in-chief Dalla-Favera and Anderson, both distinguished international researchers and leaders in the field of hematologic oncology, are overseeing an editorial board comprised of world-renowned experts who will guide the acceptance of leading blood cancer research studies from laboratories and clinics all over the world.” 

This study by Mullighan and colleagues was supported in part by the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital, the St. Baldrick’s Foundation, the Henry Schueler Foundation, the National Cancer Institute, the Dutch Cancer Society, the American Society of Hematology, the Leukemia & Lymphoma Society, the KiKa Foundation, the China Scholarship Council, the Royal Netherlands Academy of Arts and Sciences, the Princess Margaret Cancer Centre Foundation, the Ontario Institute for Cancer Research, the Canadian Institutes of Health Research, the Canadian Cancer Society Research Institute, the Terry Fox Research Institute, Genome Canada through the Ontario Genomics Institute, and the Canada Research Chair program.

Mullighan has received research grants from the following corporations: AbbVie, Loxo Oncology, and Pfizer. He has received speakers bureau honoraria from Amgen and Pfizer; and he is a member of the scientific advisory board for Illumina.

A preview issue of Blood Cancer Discovery will be available at the AACR’s Annual Meeting in April 2020. For more information or to submit a manuscript, please visit www.AACRjournals.org/bcd. To learn about the AACR’s publications program, which spans the spectrum of cancer research, please visit www.AACRjournals.org.